title: Effect of biphasic electrical current stimulation on IL-1β-stimulated annulus fibrosus cells using in vitro microcurrent generating chamber system.
abstract: METHODS
  Human annulus fibrosus (AF) cells were stimulated in vitro with interleukin (IL)-1β and exposed to biphasic electrical currents.
  
  
  OBJECTIVE
  To identify the effect of biphasic electrical currents on the production of the extracellular matrix-modifying enzymes and inflammatory mediators in IL-1β-stimulated AF cells.
  
  
  BACKGROUND
  Symptomatic disc degeneration is an important cause of chronic intractable lumbar pain and is associated with macrophage-mediated inflammation in the AF. The inflammatory reaction relationship has not been studied in the AF.
  
  
  METHODS
  Human AF cells were treated with 1 ng/mL IL-1β and cultured in a microcurrent generating chamber system. The levels of matrix metalloproteinase (MMP)-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, IL-6, IL-8, vascular endothelial growth factor (VEGF), insulin-like growth factor, and nitric oxide (NO) were measured. Expression of cyclooxygenase 2 and type I collagen mRNA was analyzed.
  
  
  RESULTS
  Compared with unstimulated cells, IL-1β-stimulated AF cells produced significantly higher levels of MMP-1, MMP-3, IL-6, IL-8, NO, and VEGF, and lower levels of TIMP-1 and TIMP-2. Exposure to a 250-mV/mm field induced time-dependent increases in IL-6, NO, MMP-1, TIMP-1, VEGF, and insulin-like growth factor-1 production. The cells exposed to 500-mV/mm field produced significantly less MMP-1, TIMP-1, IL-6, and VEGF than unexposed cells (MMP-1, 17.2 ± 4.7 ng/mL vs. 27.3 ± 3.9 ng/mL, P< 0.05; TIMP-1, 12.4 ± 3.3 ng/mL vs. 22.3 ± 2.1 ng/mL, P< 0.02; IL-6, 2.5 ± 0.9 ng/mL vs. 6.39 ± 1.90 ng/mL, P< 0.05; and VEGF, 0.1 ± 0.04 ng/mL vs. 0.44 ± 0.15 ng/mL, P< 0.03). NO production was markedly increased at 500 mV/mm (P< 0.0001).
  
  
  CONCLUSIONS
  We showed that exposure of IL-1β-stimulated AF cells to a 500 mV/mm inhibited MMP-1, IL-6, VEGF, and TIMP-1 production. The results suggest that biphasic electrical current stimulation may have efficacy in diminishing symptomatic disc degeneration.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Neurosurgery, Guro Hospital, College of Medicine, Korea University, Seoul, South Korea †Department of Medical Sciences, Graduate School of Medicine, Korea University, Seoul, South Korea ‡Seoul International School, Seoul, Korea §Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul, Korea; and ¶Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyuk
authors.initials: H
authors.lastname: Choi
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Suh
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Shin
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Hwang
authors.forename: Heung-Man
authors.initials: HM
authors.lastname: Lee
mesh_terms: D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004558:Electric Stimulation / Q000295:instrumentation* / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1